This proposal responds to the broad challenge area - Translational Science (15) and responds to the specific challenge topic - 15-MH-101: "Effect of psychotropic medications on neurodevelopment and behavior in animal models". The use of antipsychotics, antidepressants, and anti-epileptics in both pre-pubertal and post-pubertal windows of brain development raise concerns about the functional effects of psychotropic exposure. The intrauterine environment constitutes the earliest developmental milieu, thereby affording an innovative avenue by which to examine the impact of early drug exposure against a backdrop of potential individual vulnerability in offspring, prior to the onset of formally diagnosed psychopathology. Advances in medical genetics have underscored the contribution of both environmental and genetic factors in establishing developmental trajectories and, more recently, the potential importance of epigenetic alterations in predicting neurodevelopmental outcomes. Utilizing novel epigenetic methodology and established laboratory techniques in a well characterized cohort of children with laboratory confirmed and quantified fetal exposure, we will test our hypothesis that "the offspring of women with mental illness demonstrate unique epigenetic signatures indicative of the early exposure to psychotropic medications that may produce long term negative consequences for childhood functional development." Specifically, this project aims to: (1) perform a genome-wide evaluation of methylation patterns in previously collected umbilical cord blood samples (N=300) to identify genes that are differentially methylated in children whose mothers took a) antipsychotics, b) anti-epileptics, and c) antidepressant medications during their pregnancy compared to d) controls whose mothers did not take psychotropic medications;and (2) select 25 offspring within each medication exposure group with the most distinct epigenetic profiles (total N=100) to test in a laboratory paradigm evaluating current levels of hormonal, social, affective, and neurocognitive functioning. The data obtained from this 2-year proposal will provide novel insight into the epigenetic and child functioning outcomes associated with prenatal exposure to psychotropic medication.